Curcumin-loaded embryonic stem cell exosomes restored neurovascular unit following ischemia-reperfusion injury

被引:207
作者
Kalani, Anuradha [1 ]
Chaturvedi, Pankaj [1 ]
Kamat, Pradip K. [1 ]
Maldonado, Claudio [1 ,2 ]
Bauer, Philip [2 ]
Joshuaa, Irving G. [1 ]
Tyagi, Suresh C. [1 ]
Tyagi, Neetu [1 ]
机构
[1] Univ Louisville, Sch Med, Dept Physiol, Louisville, KY 40292 USA
[2] Univ Louisville, Dept Surg, Louisville, KY 40292 USA
关键词
Curcumin; Exosomes; Neurons; Stroke; CEREBRAL-ARTERY OCCLUSION; MESENCHYMAL STROMAL CELLS; BRAIN; ASTROCYTES; DISEASE; STROKE; NEURODEGENERATION; NEUROPROTECTION; MECHANISMS; MEDIATORS;
D O I
10.1016/j.biocel.2016.09.002
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
We tested whether the combined nano-formulation, prepared with curcumin (anti-inflammatory and neuroprotective molecule) and embryonic stem cell exosomes (MESC-exo(cur)), restored neurovascular loss following an ischemia reperfusion (IR) injury in mice. IR-injury was created in 8-10 weeks old mice and divided into two groups. Out of two IR-injured groups, one group received intranasal administration of MESC-exo(cur) for 7 days. Similarly, two sham groups were made and one group received MESC-exo(cur) treatment. The study determined that MESC-exo(cur) treatment reduced neurological score, infarct volume and edema following IR-injury. As compared to untreated IR group, MESC-exo(cur) treated-IR group showed reduced inflammation and N-methyl-D-aspartate receptor expression. Treatment of MESC-exo(cur) also reduced astrocytic GFAP expression and alleviated the expression of NeuN positive neurons in IR-injured mice. In addition, MESC-exocur treatment restored vascular endothelial tight (claudin-5 and occludin) and adherent (VE-cadherin) junction proteins in IR-injured mice as compared to untreated IR-injured mice. These results suggest that combining the potentials of embryonic stem cell exosomes and curcumin can help neurovascular restoration following ischemia-reperfusion injury in mice. (C) 2016 Elsevier Ltd. All rights reserved.
引用
收藏
页码:360 / 369
页数:10
相关论文
共 50 条
[1]   Bioavailability of curcumin: Problems and promises [J].
Anand, Preetha ;
Kunnumakkara, Ajaikumar B. ;
Newman, Robert A. ;
Aggarwal, Bharat B. .
MOLECULAR PHARMACEUTICS, 2007, 4 (06) :807-818
[2]  
[Anonymous], MICROVASC RES
[3]   Middle cerebral artery occlusion in the rat by intraluminal suture - Neurological and pathological evaluation of an improved model [J].
Belayev, L ;
Alonso, OF ;
Busto, R ;
Zhao, WZ ;
Ginsberg, MD .
STROKE, 1996, 27 (09) :1616-1622
[4]   Chronic NMDA administration increases neuroinflammatory markers in rat frontal cortex: Cross-talk between excitotoxicity and neuroinflammation [J].
Chang, Yunyoung C. ;
Kim, Hyung-Wook ;
Rapoport, Stanley I. ;
Rao, Jagadeesh S. .
NEUROCHEMICAL RESEARCH, 2008, 33 (11) :2318-2323
[5]   Emerging potential of exosomes and noncoding microRNAs for the treatment of neurological injury/diseases [J].
Chopp, Michael ;
Zhang, Zheng Gang .
EXPERT OPINION ON EMERGING DRUGS, 2015, 20 (04) :523-526
[6]   Evolving concepts in the triad of atherosclerosis, inflammation and thrombosis [J].
Corti, R ;
Hutter, R ;
Badimon, JJ ;
Fuster, V .
JOURNAL OF THROMBOSIS AND THROMBOLYSIS, 2004, 17 (01) :35-44
[7]  
Dai Ling-yan, 2015, Zhong Yao Cai, V38, P344
[8]   Extracellular Vesicles Improve Post-Stroke Neuroregeneration and Prevent Postischemic Immunosuppression [J].
Doeppner, Thorsten R. ;
Herz, Josephine ;
Goergens, Andre ;
Schlechter, Jana ;
Ludwig, Anna-Kristin ;
Radtke, Stefan ;
de Miroschedji, Kyra ;
Horn, Peter A. ;
Giebel, Bernd ;
Hermann, Dirk M. .
STEM CELLS TRANSLATIONAL MEDICINE, 2015, 4 (10) :1131-1143
[9]  
Fan Xiang, 2014, Adv Pharmacol, V71, P391, DOI 10.1016/bs.apha.2014.06.007
[10]   Extracellular vesicles including exosomes are mediators of signal transduction: Are they protective or pathogenic? [J].
Gangoda, Lahiru ;
Boukouris, Stephanie ;
Liem, Michael ;
Kalra, Hina ;
Mathivanan, Suresh .
PROTEOMICS, 2015, 15 (2-3) :260-271